O-SEMA-FAST: A Prospective, Non-interventional Study Investigating Oral Semaglutide Use in Adults with Type 2 Diabetes Mellitus During Ramadan

Abstract

Introduction: Oral semaglutide, a glucagon-like peptide 1 receptor agonist, requires administration on an empty stomach with up to 120 mL of water, followed by no intake of food, beverages, or other oral medications for at least 30 min to ensure optimal absorption. These instructions can be challenging to adhere to during Ramadan when patients fast for extended periods. The O-SEMA-FAST study assessed the impact of fasting on adherence to oral semaglutide dosing instructions and its subsequent effects on glycaemic control and body weight.

Methods: O-SEMA-FAST was a non-interventional, prospective study conducted in 2023 in people with type 2 diabetes mellitus (T2DM) who fasted during Ramadan and were on oral semaglutide treatment in the United Arab Emirates, Saudi Arabia, and Kuwait. Patients were followed for 20 weeks. Glycated haemoglobin (HbA1c) and body weight were measured at baseline and at the end of the study (EOS); changes were analysed by mixed models for repeated measures.

Results: Among the 257 patients included in the final analysis, there was a significant reduction in HbA1c (- 0.2%-points, p = 0.01) and a notable decrease in body weight (- 2.6 kg, p < 0.0001) from baseline to EOS. Of the 215 patients who recorded administration details in their diaries, 68.4% (n = 147) adhered to dosing instructions for ≥ 80% of diary days. Baseline mean HbA1c was 6.7% in adherent patients and 7.0% in non-adherent patients. At EOS, the change in HbA1c was - 0.3%-points (95% confidence interval, CI - 0.4, - 0.2; p < 0.0001) for adherent patients and - 0.1%-points (95% CI - 0.4, 0.1; p = 0.3) for non-adherent patients. The change in body weight was - 3.2 kg (95% CI - 4.0, - 2.4; p < 0.0001) for adherent patients and - 1.6 kg (95% CI - 2.5, - 0.8; p = 0.0001) for non-adherent patients. An increase in self-reported hypoglycaemic events (HEs) was observed, but no severe events were reported. Gastrointestinal disorders were the most common adverse effects. Among patients with available data on self-reported HEs (n = 216), 67 (31.0%) experienced HEs. The mean age, HbA1c levels and T2DM duration of patients with vs without HEs were 51.0 vs 53.3 years, 6.99 vs 6.66% and 9.2 vs 7.9 years. A greater proportion of patients experiencing HEs were treated with oral antidiabetic drugs like biguanides (90.6% vs 86.7%), sodium glucose cotransporter 2 inhibitors (85.9% vs 80.7%), sulfonylureas (32.8% vs 25.9%) and dipeptidyl peptidase 4 inhibitors (20.3% vs 11.1%).

Conclusion: The O-SEMA-FAST study demonstrated that most participants adhered to oral semaglutide instructions and experienced significant reductions in HbA1c and body weight. Overall, baseline characteristics were similar regardless of HEs; however, patients reporting HEs were younger, had higher HbA1c levels, longer T2DM duration and were under polypharmacy. Oral semaglutide is a suitable choice for individuals who fast during Ramadan, effectively controlling glycaemic levels and managing body weight while maintaining a favourable safety profile.

Trial registration: NCT05716724.

Keywords: Adherence; Body weight management; Fasting; Glucagon-like peptide 1 receptor agonist; Glycaemic control; Middle East; Oral semaglutide; Ramadan; Real-world study; Type 2 diabetes mellitus.

Fig. 1

Patient disposition. FAS full analysis set, V2.1 optional intermediate visits

Fig. 2

a Summary of crude MMRM for change from baseline in HbA1c (%) to end of follow-up visit. Covariates: baseline HbA1c, time, time squared. b Summary of adjusted MMRM for change from baseline in HbA1c (%) to end of follow-up visit). Covariates: baseline HbA1c, time, time squared, age, diabetes duration, BMI, fixed effect, sex, study site. BMI body mass index, FAS full analysis set, HbA1c glycated haemoglobin, MMRM mixed models for repeated measures, SE standard error

Fig. 3

a Relative change in mean body weight (%) from baseline to end of follow-up visit (week 20). Crude model (in-study) (MMRM). Covariates: baseline body weight, time, time squared. b Relative change in mean body weight (%) from baseline to end of follow-up visit (week 20). Adjusted model (in-study) (MMRM). Covariates: baseline body weight, time, time squared, age, diabetes duration, BMI, fixed effect, sex, study site. BMI body mass index, CI confidence interval, FAS full analysis set, MMRM mixed models for repeated measures, SE standard error

Fig. 4

a Absolute change in mean body weight (kg) from baseline to end of follow-up visit (week 20). Crude model (in-study). Covariates: baseline body weight, time, time squared. b Absolute change in mean body weight (kg) from baseline to end of follow-up visit (week 20). Adjusted model (in-study). Covariates: baseline body weight, time, time squared, age, diabetes duration, BMI, fixed effect, sex, study site. BMI body mass index, CI confidence interval, FAS full analysis set, SE standard error

Fig. 5

Adherence to oral semaglutide administration instructions. a Waited for at least 30 min after taking oral semaglutide. b Oral semaglutide on empty stomach. c Oral semaglutide with up to 120 mL of water

Fig. 6

a Negative binomial regression model for hypoglycaemic events (incidence rate between pre-Ramadan and Ramadan period). b Negative binomial regression model for hypoglycaemic events (incidence rate between Ramadan and post-Ramadan period). CI confidence interval, FAS full analysis set, IRR incidence rate ratio. O-SEMA-FAST: a prospective, non-interventional study investigating oral semaglutide use in adults with type 2 diabetes mellitus during Ramadan